Cholesterol-dependent thermotropic behavior and organization of neuronal membranes

The composition of neuronal membranes is unique with diverse lipid composition due to evolutionary requirement. The organization and dynamics of neuronal membranes are crucial for efficient functioning of neuronal receptors. We have previously established hippocampal membranes as a convenient natural source for exploring lipid-protein interactions, and organization of neuronal receptors. Keeping in mind the pathophysiological role of neuronal cholesterol, in this work, we used differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS) to explore thermotropic phase behavior and organization (thickness) of hippocampal membranes under conditions of varying cholesterol content. Our results show that the apparent phase transition temperature of hippocampal membranes displays characteristic linear dependence on membrane cholesterol content. These results are in contrast to earlier results with binary lipid mixtures containing cholesterol where phase transition temperature was found to be not significantly dependent on cholesterol concentration. Interestingly, SAXS data showed that hippocampal membrane thickness remained more or less invariant, irrespective of cholesterol content. We believe that these results constitute one of the early reports on the thermotropic phase behavior and organizational characterization of hippocampal membranes under varying cholesterol content. These results could have implications in the functioning of neuronal receptors in healthy and diseased states.